The distress thermometer as a predictor for survival in stage III lung cancer patients treated with chemotherapy

Background: Depression and Health Related Quality of Life have been associated with prognosis in lung cancer. As the Distress Thermometer measures emotional problems and may share similarities with aspects of Health Related Quality of Life, we aimed to retrospectively assess the prognostic value of the Distress Thermometer in lung cancer patients treated with chemotherapy. Methods: Patients with stage III lung cancer who were treated at the day-care oncology unit with chemotherapy containing carboplatin from 2009 to 2014 and in whom a Distress Thermometer was performed at the time of the first cycle of chemotherapy were included in this study. Results: In total, one hundred and thirteen patients were included in the analysis. In the simple Cox regression analysis, overall survival did not significantly differ according to Distress Thermometer score. No significant differences in Distress Thermometer score according to stage, histology, (intended) treatment, age, sex, and comorbidity were observed. Also in a multivariable model the Distress Thermometer was not prognostic for overall survival, whereas sex and (intended) treatment was. Conclusions: In this study no prognostic value of the Distress Thermometer could be established in patients with stage III lung cancer treated with carboplatin. Further research is warranted to address this issue

Trends in the epidemiology of small-cell lung cancer:a Dutch nationwide population-based study over 1989–2020

Introduction: This study describes the evolving characteristics of patients with small-cell lung cancer (SCLC) from 1989 to 2020 in the Netherlands to analyse how the population of patients with SCLC has changed in the last decades, hypothesising that this might explain the little progress made in SCLC. Methods: Patients with SCLC diagnosed from 1989 to 2020 were selected from the Dutch cancer registry. Incidence, patient and disease characteristics, treatments, and overall survival (OS) were analysed. Joinpoint analyses were used to test annual percentage changes for statistical significance. Results: A total of 52,527 patients were diagnosed with SCLC. The absolute numbers of patients with SCLC remained equal over the years; however, the incidence rates decreased from 15.01 to 8.93 per 100,000 person-years. The proportion of women increased from 22% to 50%, and those aged ≥75 years increased from 20% to 25%. The latter coincided with a higher proportion receiving only the best supportive care (BSC) over the years (18–24%). The use of surgery in stage I increased from 2% to 37%. The proportion of patients diagnosed with stage IV increased from 46% to 70% due to better staging. The OS improved for all stages, with a 2-year OS rate for stage IV doubling from 3% to 6%.Conclusion: The incidence of SCLC has significantly decreased over the last 30 years, with an increasing proportion of elderly and women. The male–female ratio became similar, and the OS improved. As a consequence of more elderly and probably more vulnerable patients, more patients received only the BSC.</p

Trends in the epidemiology of small-cell lung cancer:a Dutch nationwide population-based study over 1989–2020

Introduction: This study describes the evolving characteristics of patients with small-cell lung cancer (SCLC) from 1989 to 2020 in the Netherlands to analyse how the population of patients with SCLC has changed in the last decades, hypothesising that this might explain the little progress made in SCLC. Methods: Patients with SCLC diagnosed from 1989 to 2020 were selected from the Dutch cancer registry. Incidence, patient and disease characteristics, treatments, and overall survival (OS) were analysed. Joinpoint analyses were used to test annual percentage changes for statistical significance. Results: A total of 52,527 patients were diagnosed with SCLC. The absolute numbers of patients with SCLC remained equal over the years; however, the incidence rates decreased from 15.01 to 8.93 per 100,000 person-years. The proportion of women increased from 22% to 50%, and those aged ≥75 years increased from 20% to 25%. The latter coincided with a higher proportion receiving only the best supportive care (BSC) over the years (18–24%). The use of surgery in stage I increased from 2% to 37%. The proportion of patients diagnosed with stage IV increased from 46% to 70% due to better staging. The OS improved for all stages, with a 2-year OS rate for stage IV doubling from 3% to 6%.Conclusion: The incidence of SCLC has significantly decreased over the last 30 years, with an increasing proportion of elderly and women. The male–female ratio became similar, and the OS improved. As a consequence of more elderly and probably more vulnerable patients, more patients received only the BSC.</p

A population-based study describing characteristics, survival and the effect of TKI treatment on patients with EGFR mutated stage IV NSCLC in the Netherlands

INTRODUCTION: Since 2011, treatment guidelines advise targeted therapy (tyrosine kinase inhibitor, TKI) for patients with activating epidermal growth factor receptor (EGFR) mutations (EGFR+) in non-small cell lung cancer (NSCLC). We describe characteristics, first line treatment and survival of patients diagnosed with EGFR+ NSCLC in a European population, focussing on age, gender and trends over time and compare to the whole group and EGFR-. METHODS: All patients with non-squamous NSCLC stage IV, diagnosed 2011-2018, were identified from the population-based Netherlands Cancer Registry (N = 31,291). RESULTS: Among all, 7.0% were registered to be EGFR+, with highest prevalence in females 65 years to 23.6 months in the EGFR+ group <50 years treated with TKI. Over time, OS for the whole group increased by 0.6 months, of which 33% due to TKI treatment in EGFR+. The increase was strongest in females <50 years, where median OS almost doubled to 12.4 months. In the EGFR+, multivariable hazard of death was most strongly associated with the use of TKI (HR 0.45(0.41-0.49)). Of the patients with EGFR+ this space need or not, 71% received TKI treatment. Being young reduced the hazard of death (HR 0.71(95%CI:0.59-0.85)) irrespective of treatment, while male gender increased the hazard of death (HR 1.22(95%CI:1.11-1.33)). CONCLUSION: At population level, TKI treatment in patients with non-squamous NSCLC stage IV EGFR+ has very strong beneficial effects on outcome. Of the improvement in OS that was made over the years for the whole group, about one third seems to be attributed to TKI treatment in EGFR+ patients

Mutation-tailored treatment selection in non-small cell lung cancer patients in daily clinical practice

Objectives: The number of targeted drugs in non-small cell lung cancer (NSCLC) is ever-expanding and requires testing of an increasing number of predictive biomarkers. We present a comprehensive real-world evaluation of molecular testing and treatment selection in stage IV NSCLC patients in the Netherlands from 2017 to 2019. Materials and methods: Molecular pathology reports of NSCLC patients were collected from the Dutch Pathology Registry in time intervals between Oct-2017 and April-2019 (N = 5,038 patients) to study diagnostic yield. Linkage between the Dutch Pathology Registry and the Netherlands Cancer Registry enabled studying molecular testing rates for stage IV NSCLC initially diagnosed in 2017-Q4 (N = 1,193) and application of targeted therapy in stage IV NSCLC patients with potentially druggable alterations reported between Oct-2017 and June-2018 (N = 401). Results: Predictive molecular testing was performed in 85.0% of adenocarcinomas, 60.4% of NSCLC-not otherwise specified (NOS) and 17.4% of squamous cell carcinomas. Testing rates were highest for EGFR and ALK (adenocarcinoma: 82.7% and 80.7%, respectively). Incidence of molecular driver alterations (i.e. EGFR, KRAS, ALK, ROS1, BRAF, MET, ERBB2, FGFR1) was 61.1% for adenocarcinomas, 42.3% for NSCLC-NOS, and 24.7% for squamous cell carcinomas. Therapeutically relevant alterations were detected at a higher frequency by NGS- versus non-NGS-approaches (adenocarcinoma: 62.4% versus 56.5%, respectively (P = 0.004)) due to a lower failure rate, more comprehensive testing and higher sensitivity. Uptake of treatment with a registered targeted therapy in eligible patients varied per actionable target, i.e. EGFR: 85.8%, ALK: 74.7%, ROS1: 33.7%, BRAF: 51.5%. Treatment with agents in clinical studies/compassionate use was lower, i.e. MET: 22.8%, HER2: 18.9%, RET: 6.7%. Conclusion: Real-world data show NGS-based approaches to be superior to non-NGS. Uptake of molecular testing and the corresponding targeted treatments was less than expected based on guidelines and even more so for trials, off-label use and compassionate use, indicating less than optimal access to rational treatment options

Small but significant socioeconomic inequalities in axillary staging and treatment of breast cancer in the Netherlands

Background: The use of sentinel node biopsy (SNB), lymph node dissection, breast-conserving surgery, radiotherapy, chemotherapy and hormonal treatment for breast cancer was evaluated in relation to socioeconomic status (SES) in the Netherlands, where access to care was assumed to be equal. Methods: Female breast cancer patients diagnosed between 1994 and 2008 were selected from the nationwide population-based Netherlands Cancer Registry (N=176 505). Socioeconomic status was assessed based on income, employment and education at postal code level. Multivariable models included age, year of diagnosis and stage. Results: Sentinal node biopsy was less often applied in high-SES patients (multivariable analyses, ≤49 years: odds ratio (OR) 0.70 (95% CI: 0.56-0.89); 50-75 years: 0.85 (0.73-0.99)). Additionally, lymph node dissection was less common in low-SES patients aged ≥76 years (OR 1.34 (0.95-1.89)). Socioeconomic status-related differences in treatment were only significant in the age group 50-75 years. High-SES women with stage T1-2 were more likely to undergo breast-conserving surgery (radiotherapy) (OR 1.15 (1.09-1.22) and OR 1.16 (1.09-1.22), respectively). Chemotherapy use among node-positive patients was higher in the high-SES group, but was not significant in multivariable analysis. Hormonal therapy was not related to SES. Conclusion: Small but significant differences were observed in the use of SNB, lymph node dissection and breast-conserving surgery according to SES in Dutch breast cancer patients despite assumed equal access to health care

Prophylactic cranial irradiation in patients with small cell lung cancer in The Netherlands: A population-based study

Introduction: Controversy has arisen regarding the benefit of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC), particularly since the 2017 Takahashi trial publication that supports MRI surveillance in extensive-stage (ES-)SCLC. The primary aim of this study was to assess trends and determinants in PCI use over the years 2010-2018. A secondary aim was to determine contemporary practice considerations among radiation oncologists (ROs). Methods: A nationwide population-based cohort study was conducted using the Netherlands Cancer Registry data on all newly diagnosed SCLC patients (2010-2018). The change in PCI frequency over the years and determinants for PCI were analyzed using logistic regression models. Second, an online survey was performed among Dutch lung cancer ROs in 2020. Results: Among 10,264 eligible patients, 4,894 (47%) received PCI. Compared to 2010-2014, PCI use significantly decreased in 2017-2018 in ES-SCLC (OR 0.68, 95%CI 0.60-0.77) and LS-SCLC (OR 0.56, 95%CI 0.47-0.67). Incidence year, age, performance status, and thoracic radiotherapy were independent determinants for PCI. Among 41 survey participants, PCI was recommended always/sometimes/never by 22%/71%/7% in ES-SCLC and 54%/44%/2% in LS-SCLC. For ES-SCLC and LS-SCLC, 63% and 25% of ROs, respectively, confirmed influence of the Takahashi trial on PCI recommendations. Denial of such influence was associated with insufficient institutional MRI capacity. Conclusions: A significant declining trend of PCI use in both ES-SCLC and LS-SCLC was observed in The Netherlands since 2017. The Takahashi trial seems an explanation for this trend even in LS-SCLC, with differential influence of the trial depending on institutional MRI capacity. An alarming increase in practice variation regarding PCI was found which stresses the importance of ongoing trials

Non-Small-Cell Lung Cancer Patients with a High Predicted Risk of Irradical Resection: Can Chemoradiotherapy Offer Similar Survival?

Purpose: Irradical resection of non-small-cell lung cancer (NSCLC) is a detrimental prognostic factor. Recently, Rasing et al. presented an internationally validated risk score for pre-treatment prediction of irradical resection. We hypothesized that chemoradiation therapy (CRT) could serve as an alternative approach in patients with a high risk score and compared overall survival (OS) outcomes between surgery and CRT. Methods: Patients from a population-based cohort with stage IIB–III NSCLC between 2015 and 2018 in The Netherlands were selected. Patients with a ‘Rasing score’ > 4 who underwent surgery were matched with patients who underwent CRT using 1:1 nearest-neighbor propensity score matching. The primary endpoint of OS was compared using a Kaplan–Meier analysis. Results: In total, 2582 CRT and 638 surgery patients were eligible. After matching, 523 well-balanced pairs remained. Median OS in the CRT group was 27.5 months, compared with 45.6 months in the surgery group (HR 1.44, 95% CI 1.23–1.70, p < 0.001). The 114 surgical patients who underwent an R1–2 resection (21.8%) had a worse median OS than the CRT group (20.2 versus 27.5 months, HR 0.77, 95% CI 0.61–0.99, p = 0.039). Conclusion: In NSCLC patients at high predicted risk of irradical resection, CRT appears to yield inferior survival compared with surgery. Therefore, choosing CRT instead of surgery cannot solely be based on the Rasing score. Since patients receiving an R1–2 resection do have detrimental outcomes compared with primary CRT, the treatment decision should be based on additional information, such as imaging features, comorbidities, patient preference, and the surgeon’s confidence in achieving an R0 resection

Adjuvant Treatment Following Irradical Resection of Stage I-III Non-small Cell Lung Cancer: A Population-based Study

Irradical (R1-2) resection for non-small cell lung cancer (NSCLC) is associated with a dismal prognosis. Adjuvant treatment attempts to improve survival outcomes, but evidence on the optimal strategy is limited. The purpose of this study was to compare overall survival (OS) between different adjuvant treatment strategies in these patients. Out of 8,528 patients with newly diagnosed NSCLC from 2015-2018, those with an R1-2 resection were identified from the Netherlands Cancer Registry. First, OS was compared between adjuvant treatment groups 'no therapy', 'radiotherapy (RT) only', 'chemotherapy only', and 'chemo- and radiotherapy (CRT)' using multinomial propensity score-weighted Cox regression analysis. Second, three 1:1 propensity score-matched sets were created for chemotherapy vs no chemotherapy, RT only vs no therapy, and CRT vs chemotherapy only. Kaplan-Meier and Cox regression analyses for OS were performed in each set. With a median follow-up of 23 months, 427 patients were selected. In the weighted regression analysis, compared to no adjuvant therapy, chemotherapy and CRT were associated with improved OS (HR 0.41, 95%CI: 0.22-0.76; and HR 0.55, 95%CI: 0.37-0.81, respectively), whereas RT was not (HR 1.04, 95%CI: 0.73-1.50). In the matched sets, OS was improved after chemotherapy (+/- RT) compared to no chemotherapy (HR 0.47, 95%CI: 0.32-0.69). No OS difference was observed between matched groups of RT only vs no adjuvant therapy (HR 1.13, 95%CI: 0.74-1.72), nor for CRT vs chemotherapy only (HR 1.37, 95%CI: 0.70-2.71). Adjuvant chemotherapy, but not radiotherapy, improves survival after an R1-2 resection in stage I-III NSCLC

Melanoma in older patients: declining gap in survival between younger and older patients with melanoma

Background: Older people have the highest incidence of melanoma and the population in most Western countries is ageing. We evaluated how the gap in incidence and survival between younger and older patients has developed during the past decades.Material and methods: All patients diagnosed with cutaneous melanoma between 1989 and 2015 (n = 84,827) were identified from the Netherlands Cancer Registry. Elderly were defined as aged ≥70 years. Differences in patient and tumor characteristics were described, age-specific incidence rates were calculated, and relative survival (RS) and multivariable analyses estimating the Relative Excess Rate of dying (RER) were conductedResults: In older men, the melanoma age-standardized incidence increased from 18 to 103/100,000 person-years (py) between 1989 and 2015 and in older women from 23 to 70/100,000 py. In younger men and women, it increased from 8 to 21 and from 13 to 28/100,000 py, respectively. Median Breslow thickness declined from 1.8 to 1.1 mm and from 1.6 to 1.1 mm in older men and women (2003 versus 2015), and from 1.1 to 0.9 mm and 0.9 to 0.8 mm in younger men and women. In older men, 5-year RS increased from 67% (95% CI: 63%-72%) in 1989-1997 to 85% (95% CI: 83%-87%) in 2007-2015 and in older women from 81% (95% CI: 78%-85%) to 89% (95% CI: 87%-91%). In younger men and women, RS increased from 82% (95% CI: 81%-83%) to 90% (95% CI: 90%-91%) and from 92% (95% CI: 92%-93%) to 96% (95% CI: 95%-96%). After case-mix correction , older men and women no longer showed an improved survival over time (RER 2010-2015 versus 2003-2009: 0.97; 95% CI: 0.81-1.16 and 0.95; 95% CI: 0.79-1.16). Whereas in younger men and women survival remained improved (RER 0.75; 95% CI: 0.67-0.83 and 0.77; 95%CI: 0.67-0.89).Conclusion: The gap in melanoma incidence between younger and older peopl